GIP mediates the incretin effect and glucose tolerance by dual actions on α cells and β cells.
Glucose-dependent insulinotropic polypeptide (GIP) communicates nutrient intake from the gut to islets, enabling optimal levels of insulin secretion via the GIP receptor (GIPR) on β cells. The GIPR is also expressed in α cells, and GIP stimulates glucagon secretion; however, the role of this action in the postprandial state is unknown. Here, we demonstrate that GIP potentiates amino acid-stimulated glucagon secretion, documenting a similar nutrient-dependent action to that described in β cells. Moreover, we demonstrate that GIP activity in α cells contributes to insulin secretion by invoking paracrine α to β cell communication. Last, specific loss of GIPR activity in α cells prevents glucagon secretion in response to a meal stimulus, limiting insulin secretion and driving glucose intolerance. Together, these data uncover an important axis by which GIPR activity in α cells is necessary to coordinate the optimal level of both glucagon and insulin secretion to maintain postprandial homeostasis.
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Related Subject Headings
- Receptors, Gastrointestinal Hormone
- Receptors, G-Protein-Coupled
- Incretins
- Humans
- Glucose
- Glucagon
- Gastric Inhibitory Polypeptide
- Diabetes Mellitus, Type 2
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Location
Related Subject Headings
- Receptors, Gastrointestinal Hormone
- Receptors, G-Protein-Coupled
- Incretins
- Humans
- Glucose
- Glucagon
- Gastric Inhibitory Polypeptide
- Diabetes Mellitus, Type 2